RiteMED Cloxacillin Mechanism of Action

Pharmacology: Mechanism of Action: Cloxacillin is an acid- and penicillinase-resistant isoxazolylpenicillin bactericidal antibiotic. It resists the action of bacterial penicillinase because the steric hindrance offered by its acyl side chain prevents penicillinase from attacking and opening the β-lactam ring, whose integrity is necessary for antibacterial activity.
Cloxacillin exerts its bactericidal activity by interfering with the synthesis of the bacterial cell wall. It binds to penicillin-binding proteins responsible for the synthesis of peptidoglycan, a heteropolymeric structure that gives the cell wall its mechanical stability. The final stage of peptidoglycan synthesis involves the completion of the cross-linking with the terminal glycine residue of the pentaglycine bridge linking to the 4th residue of the pentapeptide. The transpeptidase that performs this step is inhibited by penicillins. The bacterial cell wall, thus weakened, leads to swelling and rupture of the microorganism resulting in bacterial death.
Microbiology: Spectrum of Activity: Cloxacillin is active against many penicillinase-producing strains of Staphylococcus aureus, Streptococcus epidermidis, Streptococcus pyogenes, Streptococcus pneumoniae and Streptococcus viridans. It is also active against gram-positive bacilli but not against Streptococcus faecalis.
Pharmacokinetics: Cloxacillin is resistant to inactivation in the presence of acidic gastric secretions and is rapidly but incompletely absorbed from the GIT.
Cloxacillin is distributed into the liver, kidneys, synovial, pleural and ascitic fluids, bone and bile. In a child with septic arthritis who received oral 500 mg every 6 hrs, cloxacillin concentrations in serum and in synovial fluids were 7.7 and 3.8 mcg/mL, respectively, in samples obtained 2 hrs after a dose.
Like other penicillins, only minimal concentrations of cloxacillin are attained in cerebrospinal fluid.
Cloxacillin is 90-96% bound to serum proteins.
Cloxacillin is partially metabolized to active and inactive metabolites. Cloxacillin is also hydroxylated to a small extent to a microbiologically active metabolite which appears to be as active as cloxacillin.
Cloxacillin and its metabolites are rapidly excreted in urine mainly by tubular secretion and glomerular filtration. It is also partly excreted in feces via biliary elimination.
Cloxacillin's serum half-life is slightly prolonged in patients with impaired renal function and ranges from 0.8-2.3 hrs in patients with severe renal impairment.
Cloxacillin is only minimally removed by hemodialysis or peritoneal dialysis.